Rapid multistep kinetic model generation from transient flow data

被引:84
作者
Hone, Christopher A. [1 ,2 ]
Holmes, Nicholas [1 ,2 ]
Akien, Geoffrey R. [1 ,2 ,3 ]
Bourne, Richard A. [1 ,2 ]
Muller, Frans L. [1 ,2 ]
机构
[1] Univ Leeds, Sch Chem, Inst Proc Res & Dev, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Leeds, Sch Chem & Proc Engn, Leeds LS2 9JT, W Yorkshire, England
[3] Univ Lancaster, Dept Chem, Lancaster LA1 4YB, England
基金
英国工程与自然科学研究理事会;
关键词
AXIAL-DISPERSION; LAMINAR-FLOW; HELICAL-COILS; MICROREACTORS; DESIGN; MERITS; NUMBER; TUBES;
D O I
10.1039/c6re00109b
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Today, the generation of kinetic models is still seen as a resource intensive and specialised activity. We report an efficient method of generating reaction profiles from transient flows using a state-of-the-art continuous-flow platform. Experimental data for multistep aromatic nucleophilic substitution reactions are collected from an automated linear gradient flow ramp with online HPLC at the reactor outlet. Using this approach, we generated 16 profiles, at 3 different inlet concentrations and 4 temperatures, in less than 3 hours run time. The kinetic parameters, 4 rate constants and 4 activation energies were fitted with less than 4% uncertainty. We derived an expression for the error in the observed rate constants due to dispersion and showed that such error is 5% or lower. The large range of operational conditions prevented the need to isolate individual reaction steps. Our approach enables early identification of the sensitivity of product quality to parameter changes and early use of unit operation models to identify optimal process-equipment combinations in silico, greatly reducing scale up risks.
引用
收藏
页码:103 / 108
页数:6
相关论文
共 33 条
[1]   On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system [J].
Adamo, Andrea ;
Beingessner, Rachel L. ;
Behnam, Mohsen ;
Chen, Jie ;
Jamison, Timothy F. ;
Jensen, Klavs F. ;
Monbaliu, Jean-Christophe M. ;
Myerson, Allan S. ;
Revalor, Eve M. ;
Snead, David R. ;
Stelzer, Torsten ;
Weeranoppanant, Nopphon ;
Wong, Shin Yee ;
Zhang, Ping .
SCIENCE, 2016, 352 (6281) :61-67
[2]   Using Continuous Processes to Increase Production [J].
Anderson, Neal G. .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2012, 16 (05) :852-869
[3]   ON THE DISPERSION OF A SOLUTE IN A FLUID FLOWING THROUGH A TUBE [J].
ARIS, R .
PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES A-MATHEMATICAL AND PHYSICAL SCIENCES, 1956, 235 (1200) :67-77
[4]   Reaction progress kinetic analysis: A powerful methodology for mechanistic studies of complex catalytic reactions [J].
Blackmond, DG .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (28) :4302-4320
[5]   EXPERIMENTAL STUDY OF PHYSICAL MECHANISMS [J].
BOX, GEP ;
HUNTER, WG .
TECHNOMETRICS, 1965, 7 (01) :23-&
[6]  
Dallin, 2011, J AM CHEM SOC, V133, P3601
[7]   Thermolysis of 1,3-dioxin-4-ones: fast generation of kinetic data using in-line analysis under flow [J].
Durand, Thomas ;
Henry, Cyril ;
Bolien, David ;
Harrowven, David C. ;
Bloodworth, Sally ;
Franck, Xavier ;
Whitby, Richard J. .
REACTION CHEMISTRY & ENGINEERING, 2016, 1 (01) :82-89
[8]  
Gelhausen M. G., 2014, MIXING HEAT TRANSFER
[9]   Alkylation of Substituted Benzoic Acids in a Continuous Flow Microfluidic Microreactor: Kinetics and Linear Free Energy Relationships [J].
Gholamipour-Shirazi, Azarmidokht ;
Rolando, Christian .
ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2012, 16 (05) :811-818
[10]   Continuous-Flow TechnologyA Tool for the Safe Manufacturing of Active Pharmaceutical Ingredients [J].
Gutmann, Bernhard ;
Cantillo, David ;
Kappe, C. Oliver .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (23) :6688-6728